TLR4 is required for the obesity-induced pancreatic beta cell dysfunction

Juan,; Li, Qing; Lei, Chi‐Un; Chen, Guihai; Ye, Jianhuai; Zhang, Bo; Weiping,; Wenyan,; Yi, Mingdong; Qin, Qin; Jin, Jin; Da-jin,; Zou,

doi:10.1093/abbs/gmt149

Cited by 5 publications

(5 citation statements)

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“…In our study we observed marked increase in the percentage of late apoptotic β‐cells in chronic HFD mice, signifying the deleterious effect of high fat upon the survival of β‐cells. TLR4 is necessary for obesity‐induced pancreatic β‐cell dysfunction (Li et al, 2013). In this context, a recent publication showed that TLR4 blocks replication of pancreatic β‐cells during diet‐induced obesity (Ji et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Fetuin‐A excess expression amplifies lipid induced apoptosis and β‐cell damage

Mukhuty

Fouzder

Kundu

2021

Journal Cellular Physiology

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Fetuin-A, a hepato-adipokine, is associated with lipid-mediated islet inflammation and inflicts β-cell death but the underlying mechanisms are still unclear. In an earlier report, it was shown that fetuin-A promotes lipid-induced insulin resistance by acting as an endogenous ligand of toll like receptor 4. Recently, we have also reported that β-cells secrete fetuin-A on stimulation by palmitate causing β-cell dysfunction. The aim of this study was twofold: (a) screening the role of fetuin-A in survival of murine β-cells, and (b) to validate the effect of fetuin-A release and lipid induced apoptosis in mouse insulinoma cell line MIN6. Excess of lipid and fetuin-A in circulation induced significant deterioration of islet histoarchitecture and impeded insulin secretion by 2.7 ± 0.5-folds in 20 weeks high fat diet mice. Administration of fetuin-A (0.7 mg/g) along with 4 weeks of HFD produced similar results as 20 weeks of high fat feeding. Treating high doses of palmitate alone (0.50 mM) as well as in combination with fetuin-A (100 µg/ml) for 24 h inflicted apoptosis in MIN6 through the mitochondrial pathway. Knockdown of fetuin-A gene partially inhibited palmitate inflicted apoptosis in MIN6 by 1.83 ± 0.25 times, however, fetuin-A when added in the medium caused re-emergence of apoptosis. Notably, apoptosis induced by palmitate conditioned media from MIN6, 3T3L1, and HepG2, was partially inhibited in fetuin-A KD MIN6. These results confirmed the critical role of circulatory fetuin-A and β-cell secreted fetuin-A in β-cell dysfunction and apoptosis under hyperlipidemic conditions.

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Section: Discussionmentioning

confidence: 99%

Fetuin‐A excess expression amplifies lipid induced apoptosis and β‐cell damage

Mukhuty

Fouzder

Kundu

2021

Journal Cellular Physiology

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“…β-cells respond to palmitate via TLR4/MyD88 pathway and produce chemokines that recruit M1-type proinflammatory monocytes/ macrophages to the islets [151]. High fat diet-induced obesity stimulates TLR4 up-regulation in pancreatic β-cells, and lead to the recruitment of macrophage into pancreatic islet, which finally results in pancreatic β-cell dysfunction [152].…”

Section: Tlr4mentioning

confidence: 99%

Emerging Role of Pancreatic β-Cells during Insulin Resistance

Mukhuty¹,

Fouzder²,

Das³

et al. 2019

Type 2 Diabetes [Working Title]

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In today's world, type 2 diabetes has become a part of every household and leads to various complications including high blood sugar level, diabetic retinopathy, diabetic foot, diabetic nephropathy and diabetic neuropathy. Yet people lack awareness about this disease and its detrimental effects. For a better understanding of this disease we must know about the causes and preventive measures since the medications used in treating type 2 diabetes have moderate to severe side effects. Type 2 diabetes is characterized by loss of insulin receptor activity in skeletal muscle and adipocytes, compensatory insulin secretion from pancreatic β-cells, β-cell dysfunction and death. The proper functioning of β-cells is a major criterion for preventing advent of type 2 diabetes. The different natural or physiological insulin secretagogues include glucose, amino acids and fatty acids, which stimulate insulin secretion under the influence of various hormones like incretins, leptin, growth hormone, melatonin and estrogen. However, excess of nutrients lead to β-cell dysfunction and dearth of insulin involving various signal molecules like SIRT1, PPARγ, TLR4, NF-ΚB, Wnt, mTOR, inflammasomes, MCP1, EGFR, and Nrf2. A deeper insight into the functioning of these signaling molecules will also create new avenues for therapeutic interventions of curing β-cell dysfunction and death.

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“…Once activated, TLR4 launches a cascade of immune responses that end up activating Nuclear factor kappa B (NF-B) either through a myeloid differentiation factor 88 (MyD88)dependent or -independent pathway [2]. Several studies in the literature already suggest that TLR4 and its downstream regulators (such as MyD88) play a role in energy and glucose homeostasis For example, animals lacking a functional TLR4 are relatively protected from high fat diet-induced obesity and diabetes [14][15][16][17][18]. Interestingly, animals lacking TLR5which is mainly MyD88 dependent-are at increased risk for obesity [19].…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects

Haija

Chu

et al. 2021

Surgery for Obesity and Related Diseases

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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TLR4 is required for the obesity-induced pancreatic beta cell dysfunction

Cited by 5 publications

References 0 publications

Fetuin‐A excess expression amplifies lipid induced apoptosis and β‐cell damage

Fetuin‐A excess expression amplifies lipid induced apoptosis and β‐cell damage

Emerging Role of Pancreatic β-Cells during Insulin Resistance

Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects

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